Women and Epilepsy

Question 1

How might long term use of antiseizure medication affect bone health?

Answer 1

May reduce bone density and vitamin D levels, particularly is enzyme inducing and sodium valproate

Also at increased risk of:
▪️ Osteomalacia
▪️ Osteoporosis
▪️ Fractures

Question 2

What risk factors place a woman at higher risk of losing bone density on ASM?

Answer 2

▪️ Living in the UK where vitamin D levels are already low
▪️ Women already have lower bone density than men
▪️ Bone density reduces following menopause

Question 3

How can you be proactive about optimising bone health in the management of women with epilepsy?

Answer 3

Consider vitamin D and calcium supplements, as well as dietary and lifestyle advice

Question 4

Which medications are associated with the highest risk of fractures and lower bone density?

Answer 4

▪️ Phenobarbital
▪️ Carbamazepine
▪️ Clonazepam
▪️ Sodium valproate

Question 5

What can you conduct if someone with epilepsy is at risk of osteoporosis?

Answer 5

A fracture risk assessment using:
▪️ FRAX tool
▪️ QFracture tool

Question 6

What is catamenial epilepsy?

Answer 6

The cyclic exacerbation of seizures in relation to the menstrual cycle

Question 7

When are seizures most likely to occur during the menstrual cycle?

Answer 7

When progesterone levels drop

Question 8

What are the three commonly recognised patterns of catamenial seizures?

Answer 8

▪️ C1 = Perimenstrual (Day -3 to +3)
▪️ C2 = Peri-ovulatory (Day 10 to 13)
▪️ C3 = Entire luteal phase in anovulatory cycles (Day 10 to 3)

Question 9

What could you consider in the management of catamenial seizures?

Answer 9

▪️ Additional medication during at-risk periods (e.g., benzodiazepines) (BUT cannot take long-term)
▪️ Contraception (e.g., pessaries)

Question 10

What should you consider when prescribing contraception to women with epilepsy?

Answer 10

▪️ Effect of ASM on contraceptive efficacy
▪️ Effect on contraception on ASM levels

Question 11

What epilepsy medications are associated with higher contraceptive failure?

Answer 11

Enzyme inducing ASM

Question 12

What must you consider when a woman with epilepsy stops taking contraception?

Answer 12

If ASM levels were reduced by the contraceptive so dose was increased, this may then become toxic on cessation of contraceptive

Question 13

What factors may contribute to the slight reduction in fertility seen with epilepsy?

Answer 13

▪️ Associated morbidities
▪️ Social factors
▪️ ASM effects on libido or polycystic ovary syndrome
▪️ Personal choice

Question 14

What is essential when a woman with epilepsy wants to have a baby preconception?

Answer 14

▪️ Planned pregnancy
▪️ Folic acid supplements
▪️ ASM review - may need to adjust to minimise teratogenic risk whilst keeping mother safe

Question 15

What should be consider when a woman with epilepsy is pregnant?

Answer 15

▪️ Regular monitoring of both mother and foetus to maximise safety
▪️ Monitor ASM levels
▪️ Small risk of seizures during labour

Question 16

What factors should be considered postpartum for women with epilepsy?

Answer 16

▪️ Depression or fear of seizure when holding or caring for baby
▪️ Sleep-deprivation worsening seizures
▪️ Breastfeeding - generally okay if not on high doses of phenobarbital (watch for drowsiness or withdrawal signs in baby)

Question 17

What poor outcomes are women with epilepsy at higher risk for when pregnant?

Answer 17

▪️ Major malformations
▪️ Minor malformations
▪️ Lower birth weight
▪️ Developmental delay/ASD/LD
▪️ Injury or falls increasing risk of miscarriage
▪️ SUDEP

Question 18

What factors may be considered when a women with epilepsy is deciding to have children?

Answer 18

▪️ Risk of offspring inheriting epilepsy or related condition
▪️ Risk of pregnancy complications
▪️ Risk of teratogenicity from ASM
▪️ Control of epilepsy during pregnancy (risk of seizures or status?)
▪️ Ability of mother/family to look after baby if epilepsy is uncontrolled

Question 19

What is the risk of inheriting epilepsy?

Answer 19

▪️ Different depending on underlying condition
▪️ Generally low risk, but higher than general population
▪️ If genetic basis is know, consider incomplete penetrance and variable severity

Question 20

What medications are the safest for women of childbearing age?

Answer 20

▪️ Lamotrigine
▪️ Levetiracetam
▪️ Oxcarbazepine

Question 21

What must be considering when prescribing sodium valproate?

Answer 21

▪️ Women must be very careful not to fall pregnant on it
▪️ Have to sign form understanding the risks
▪️ Must be using the implant or coil contraceptive so cannot be forgotten (or had uterus removed)

Question 22

What factors increase the risk of epilepsy being passed on to the child?

Answer 22

▪️ Greater if mother has epilepsy compared to the father
▪️ Greater if child is female
▪️ Idiopathic generalised epilepsy (compared to focal)
▪️ Onset of epilepsy before age 20
▪️ Potentially higher if both parents have epilepsy

Question 23

What pregnancy complications are women with epilepsy, particularly on AEDS, at higher risk of?

Answer 23

▪️ Induction
▪️ Caesarean section
▪️ Post-partum haemorrhage
▪️ Infant with Apgar score lower than 7 (general health of newborn)
▪️ Severe pre-eclampsia
▪️ Bleeding early on
▪️ Offspring malformations

Question 24

What teratogenic effects can AEDs have on the foetus?

Answer 24

▪️ Foetal loss
▪️ Intrauterine growth retardation
▪️ Congenital malformations
▪️ Impaired postnatal development
▪️ Behavioural problems

Question 25

What is the relationship between sodium valproate and risk of foetus malformation?

Answer 25

Dose-dependent - it increased with higher doses

e.g., 6.7% of pregnancies on 400mg
54.5% on more than 2800mg

Question 26

Is there a recurrence risk of congenital malformations in infants exposed to AEDs in utero?

Answer 26

Yes - 16.8% risk for those who’s first child had malformations compared to 9.8% for those who’s didn’t

Genetic influence?

Question 27

What can you do to reduce the risk of pregnancy complications and malformations from in utero AED exposure?

Answer 27

▪️ Adjust or change medication, particularly in those with a history of malformation
▪️ Consider monotherapy as opposed to polytherapy
▪️ BUT careful not to compromise safety of the mother

Question 28

What factors are associated with increased likelihood of seizures occurring/worsening in pregnancy?

Answer 28

▪️ Greater preconception seizure frequency
▪️ Changes in behaviour
▪️ Biological changes leading to increase clearance of some ASM

Question 29

How does presence of seizures in the 2 years before pregnancy effect risk of seizures during pregnancy and labour?

Answer 29

Increases the risk

With seizures in year before = 75.2%
Without seizures in year before = 19.8%

Question 30

How might seizure risk change during pregnancy in those with catamenial epilepsy?

Answer 30

Its appears to decrease (gets better!)

Question 31

Which ASM show significant drops in levels during pregnancy and what is the risk associated with this?

Answer 31

▪️ Lamotrigine, oxcarbazepine, levetiracetam
▪️ Must be careful when increasing dose to compensate as may induce toxicity following birth

Question 32

What happens to lamotrigine plasma levels during and after pregnancy?

Answer 32

▪️ Evidence it decreases during pregnancy, risking loss of seizure control
▪️ May increase rapidly following birth, risking dose-related AEs

Question 33

What happens to levetiracetam plasma levels during pregnancy?

Answer 33

Appear to decrease, particularly in the third trimester

Question 34

What happens to oxcarbazepine plasma levels during pregnancy?

Answer 34

Levels of the active metabolite (MHD) may decrease gradually

Question 35

What is the best predictor of seizure control during pregnancy?

Answer 35

How well it was controlled before pregnancy

Question 36

What is the second most common indirect cause of maternal death?

Answer 36

Neurological causes such as epilepsy and stroke

Question 37

How has maternal mortality due to SUDEP changed in recent years?

Answer 37

Statistically significant increase

Low proportion of women whose medications are optimised before or during pregnancy - lower standard of care?

Question 38

What is the government guidelines for prescribing valproate to women?

Answer 38

▪️ Cannot be prescribed unless there is a pregnancy prevention programme in place
▪️ Signed risk acknowledgement form at least annually
▪️ Banned for migraines and bipolar during pregnancy
▪️ Banned for epilepsy during pregnancy unless no other effective treatment